We propose studying the changing of protein modification that occurs on a number of lysosomal enzymes during differentiation. The dictyostelial lysosome has been considered an excellent model for the lysosomes of higher organisms. The alteration of protein modification structure affects the configuration of these lysosomal enzymes and could affect enzymatic properties, in vivo stability, and secretion. This "retooling" of preexisting molecules represents a means to rapidly alter the organelle during the process of differentiation. We will characterize the alterations occuring to the enzymes and determine how the alterations affect the fate of the various enzymes. Human congenital diseases such as l-cell disease, Fabry's disease, Niemann-Pick disease, and Gaucher's disease have been shown to be due to deficiencies in lysosomal enzymes. We expect this grant to give information relating to what characteristics of post-translational modification are needed to protect a lysosomal enzyme from being degraded within the lysosome. Such information would be valuable in enzyme replacement therapy to correct a lysosomal enzyme deficiency. The incoming replacement enzyme needs to be stable within the lysosome for an extended period of time.